CD22 is a cell-surface type I glycoprotein of the sialoadhesin family. CD22 is also known in the art as BL-CAM, B3, Leu-14 and Lyb-8, among other names. CD22 was initially characterized by the antibodies anti-S-HCL-1 (Schwarting, R. et al. (1985) Blood 65:974-983), HD39 (Dorken, B. et al. (1986) J. Immunol. 136:4470-4479) and RFB4 (Campana, D. et al. (1985) J. Immunol. 134:1524-1530). CD22 has been established as a lectin-like adhesion molecule that binds alpha2,6-linked sialic acid-bearing ligands and as a regulator of B cell antigen receptor (BCR) signaling. Structurally, there are several splice variants of CD22 that exist, but the predominant form in humans has an extracellular region containing seven immunoglobulin-like domains.
CD22 has been shown to be specifically expressed by B lymphocytes and is functionally important as a negative regulator of B lymphocyte activation (reviewed by Nitschke, L. (2005) Curr. Opin. Immunol. 17:290-297 and Tedder, T. F. et al (2005) Adv. Immunol. 88:1-50). In studies that utilized gene-targeted mice that expressed mutant CD22 molecules that do not interact with alpha2,6-linked sialic acid ligands, it was determined that certain functions (such as expression of cell surface CD22, IgM and MHC Class II on mature B cells, maintenance of marginal zone B cell populations, optimal B cell antigen receptor-induced proliferation and B cell turnover rates) were regulated by CD22 ligand binding, whereas other functions (such as CD22 phosphorylation, CD22 negative regulation of calcium mobilization after BCR ligation, recruitment of SHP-1 to CD22 and B cell migration) did not require ligand engagement (Poe, J. C. et al. (2004) Nat. Immunol. 5:1078-1087).
CD22 is considered to be an inhibitory co-receptor that downmodulates BCR signaling by setting a signaling threshold that prevents overstimulation of B cells. Activation of such an inhibitory co-receptor occurs by phosphorylation on cytoplasmic ITIMs (immunoreceptor tyrosine-based inhibition motifs), followed by recruitment of the tyrosine phosphatase SHP-1 or the lipid phosphatase SHIIP (reviewed in by Nitschke, L. (2005) Curr. Opin. Immunol. 17:290-297). Additionally, CD22 has been found to play a central role in a regulatory loop controlling the CD19/CD21-Src-family protein tyrosine kinase (PTK) amplification pathway that regulates basal signaling thresholds and intensifies Src-family kinase activation after BCR ligation (reviewed in Tedder, T. F. et al (2005) Adv. Immunol. 88:1-50).
Approximately 60-80% of B cell malignancies express CD22, thereby making it a potential target for passive immunotherapy (see e.g., Cesano, A. and Gayko, U. (2003) Semin. Oncol. 30:253-257). Moreover, selective modulation of B cell activity via targeting of CD22 has been suggested as a means for treatment of autoimmune diseases (see e.g., Steinfeld, S. D. and Youinou, P. (2006) Expert. Opin. Biol. Ther. 6:943-949). A humanized anti-CD22 monoclonal antibody, epratuzumab, has been described (Coleman, M. et al. (2003) Clin. Cancer Res. 9:3991S-3994S). However, additional anti-CD22 reagents are still needed.